Treatment of Deep Cartilage Defects in the Knee with Autologous Chondrocyte Transplantation

University of Gothenburg, Goeteborg, Västra Götaland, Sweden
New England Journal of Medicine (Impact Factor: 55.87). 11/1994; 331(14):889-95. DOI: 10.1056/NEJM199410063311401
Source: PubMed


Full-thickness defects of articular cartilage in the knee have a poor capacity for repair. They may progress to osteoarthritis and require total knee replacement. We performed autologous chondrocyte transplantation in 23 people with deep cartilage defects in the knee.
The patients ranged in age from 14 to 48 years and had full-thickness cartilage defects that ranged in size from 1.6 to 6.5 cm2. Healthy chondrocytes obtained from an uninvolved area of the injured knee during arthroscopy were isolated and cultured in the laboratory for 14 to 21 days. The cultured chondrocytes were then injected into the area of the defect. The defect was covered with a sutured periosteal flap taken from the proximal medial tibia. Evaluation included clinical examination according to explicit criteria and arthroscopic examination with a biopsy of the transplantation site.
Patients were followed for 16 to 66 months (mean, 39). Initially, the transplants eliminated knee locking and reduced pain and swelling in all patients. After three months, arthroscopy showed that the transplants were level with the surrounding tissue and spongy when probed, with visible borders. A second arthroscopic examination showed that in many instances the transplants had the same macroscopic appearance as they had earlier but were firmer when probed and similar in appearance to the surrounding cartilage. Two years after transplantation, 14 of the 16 patients with femoral condylar transplants had good-to-excellent results. Two patients required a second operation because of severe central wear in the transplants, with locking and pain. A mean of 36 months after transplantation, the results were excellent or good in two of the seven patients with patellar transplants, fair in three, and poor in two; two patients required a second operation because of severe chondromalacia. Biopsies showed that 11 of the 15 femoral transplants and 1 of the 7 patellar transplants had the appearance of hyaline cartilage.
Cultured autologous chondrocytes can be used to repair deep cartilage defects in the femorotibial articular surface of the knee joint.

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    • "The adult articular cartilage has a limited ability for self-repair[1]as a result of the absence of vascularization in this highly specialized tissue. Options to provide reparative cells in sites of cartilage lesions include autologous chondrocyte implantation and marrow-stimulating techniques to recruit chondroregenerative bone marrow-derived mesenchymal stem cells (MSCs)234but the outcome of such procedures do not meet the original hyaline cartilage as the repair tissue is commonly made of a fibrocartilaginous structure (type-I collagen instead of type-II collagen proteoglycans) of lesser mechanical quality and that does not integrate with the adjacent, original cartilage[5]. A promising approach might be to conveniently supply the lesions with bone marrow concen- trates[6]composed of chondrogenically competent MSCs (~1%) that specifically commit towards the chondrocyte phenotype under adapted treatment conditions among other cell populations (haematopoietic progenitor cells, haematopoietic cells, fibroblasts)[7,8]rather than using isolated progenitors that necessitate more complex steps of preparation and expansion[6]. "
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    ABSTRACT: Genetic modification of marrow concentrates may provide convenient approaches to enhance the chondrogenic differentiation processes and improve the repair capacities in sites of cartilage defects following administration in the lesions. Here, we provided clinically adapted recombinant adeno-associated virus (rAAV) vectors to human bone marrow aspirates to promote the expression of the potent transforming growth factor beta (TGF-beta) as a means to regulate the biological and chondrogenic activities in the samples in vitro. Successful TGF-beta gene transfer and expression via rAAV was reached relative to control (lacZ) treatment (from 511.1 to 16.1 pg rhTGF-beta/mg total proteins after 21 days), allowing to durably enhance the levels of cell proliferation, matrix synthesis, and chondrogenic differentiation. Strikingly, in the conditions applied here, application of the candidate TGF-beta vector was also capable of reducing the hypertrophic and osteogenic differentiation processes in the aspirates, showing the potential benefits of using this particular vector to directly modify marrow concentrates to generate single-step, effective approaches that aim at improving articular cartilage repair in vivo.
    Full-text · Article · Jan 2016 · Journal of Cellular and Molecular Medicine
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    • "Cellular and tissue-engineering therapies are considered the best options for the repair of many cartilage defects. In accordance with this, autologous and allogeneic chondrocytes are grafted into articular cartilage lesions with fair clinical outcomes (Brittberg et al., 1994; Jiang et al., 2011; Cucchiarini et al., 2014). Research is also under way to find compatible implants for facial, laryngeal and tracheal reconstruction, with some advances already being made in the clinical setting (Yanaga et al., 2009; Fabre et al., 2013). "
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    ABSTRACT: Advances in animal transgenesis may allow using xenogeneic chondrocytes in tissue-engineering applications for clinical cartilage repair. Porcine cartilage is rejected by humoral and cellular mechanisms that could be overcome by identifying key molecules triggering rejection and developing effective genetic-engineering strategies. Accordingly, high expression of α1,2-fucosyltransferase (HT) in xenogeneic cartilage protects from galactose α1,3-galactose (Gal)-mediated antibody responses. Now, we studied whether expression of a complement inhibitor provides further protection. First, porcine articular chondrocytes (PAC) were isolated from non-transgenic, single and double transgenic pigs expressing HT and moderate levels of human CD59 (hCD59) and their response to human serum was assessed. High recombinant expression of human complement regulatory molecules hCD59 and hDAF was also attained by retroviral transduction of PAC for further analyses. Complement activation on PAC after exposure to 20 % human serum for 24 hours mainly triggered the release of pro-inflammatory cytokines IL-6 and IL-8. Transgenic expression of HT and hCD59 did not suffice to fully counteract this effect. Nevertheless, the combination of blocking anti-Gal antibodies (or C5a) and high hCD59 levels conferred very high protection. On the contrary, high hDAF expression attained the most dramatic reduction in IL-6/IL-8 secretion by a single strategy, but the additional inhibition of anti-Gal antibodies or C5a did not provide further improvement. Notably, we demonstrate that both hCD59 and hDAF inhibit anaphylatoxin release in this setting. In conclusion, our study identifies genetic-engineering approaches to prevent humoral rejection of xenogeneic chondrocytes for use in cartilage repair.
    Full-text · Article · Nov 2015 · European cells & materials
    • "In recent years, there has been increased interest in the use of cell-and tissue-engineering based therapies for the treatment of focal cartilage defects (Brittberg et al., 1994; Temenoff and Mikos, 2000). While significant progress has been made in this field, realising an efficacious therapeutic option for the treatment of OA remains elusive and is considered to be one of the greatest challenges in the field of orthopaedic medicine. "
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    ABSTRACT: Arthroplasty is currently the only surgical procedure available to restore joint function following articular cartilage and bone degeneration associated with diseases such as osteoarthritis (OA). A potential alternative to this procedure would be to tissue-engineer a biological implant and use it to replace the entire diseased joint. The objective of this study was therefore to tissue-engineer a scaled-up, anatomically shaped, osteochondral construct suitable for partial or total resurfacing of a diseased joint. To this end it was first demonstrated that a bone marrow derived mesenchymal stem cell seeded alginate hydrogel could support endochondral bone formation in vivo within the osseous component of an osteochondral construct, and furthermore, that a phenotypically stable layer of articular cartilage could be engineered over this bony tissue using a co-culture of chondrocytes and mesenchymal stem cells. Co-culture was found to enhance the in vitro development of the chondral phase of the engineered graft and to dramatically reduce its mineralisation in vivo. In the final part of the study, tissue-engineered grafts (~ 2 cm diameter) mimicking the geometry of medial femorotibial joint prostheses were generated using laser scanning and rapid prototyped moulds. After 8 weeks in vivo, a layer of cartilage remained on the surface of these scaled-up engineered implants, with evidence of mineralisation and bone development in the underlying osseous region of the graft. These findings open up the possibility of a tissueengineered treatment option for diseases such as OA.
    No preview · Article · Sep 2015 · European cells & materials
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